Clinical and CT characteristics of Xpert MTB/RIF-negative pulmonary tuberculosis

Purpose To determine the diagnostic accuracy of the Xpert MTB/RIF assay in patients with smear-negative pulmonary tuberculosis (TB) and to assess clinical and CT characteristics of Xpert-negative pulmonary TB. Material and methods We retrospectively reviewed the records of 1,400 patients with suspected pulmonary TB for whom the sputum Xpert MTB/RIF assay was performed between September 1, 2014 and February 28, 2020. Clinical and CT characteristics of smear-negative pulmonary TB patients with negative Xpert MTB/RIF results were compared with positive results. Results Of 1,400 patients, 365 (26.1%) were diagnosed with pulmonary TB and 190 of 365 patients (52.1%) were negative for sputum acid-fast bacilli. The diagnosis of pulmonary TB was based on a positive culture, positive Xpert MTB/RIF or the clinical diagnoses of patients treated with an anti-TB medication. The sensitivity, specificity, positive predictive and negative predictive values of sputum Xpert MTB/RIF for smear-negative pulmonary TB were 41.1%, 100%, 100%, and 90.1%, respectively. Finally, 172 patients with smear-negative pulmonary TB who underwent chest CT within 2 weeks of diagnosis were included to compare Xpert-positive (n = 66) and Xpert- negative (n = 106) groups. Patients with sputum Xpert-negative TB showed lower positive rates for sputum culture (33.0% vs. 81.8%, p<0.001) and bronchoalveolar lavage culture (53.3% vs. 84.6%, p = 0.042) than in Xpert-positive TB. Time to start TB medication was longer in patients with Xpert-negative TB than in Xpert-positive TB (11.3±16.4 days vs. 5.0±8.7 days, p = 0.001). On chest CT, sputum Xpert-negative TB showed significantly lower frequency of consolidation (21.7% vs. 39.4%, p = 0.012), cavitation (23.6% vs. 37.9%, p = 0.045), more frequent peripheral location (50.9% vs. 21.2 p = 0.001) with lower area of involvement (4.3±4.3 vs. 7.6±6.4, p<0.001). Multivariate analysis revealed peripheral location (odds ratios, 2.565; 95% confidence interval: 1.157–5.687; p = 0.020) and higher total extent of the involved lobe (odds ratios, 0.928; 95% confidence interval: 0.865–0.995; p = 0.037) were significant factors associated with Xpert MTB/RIF-negative TB. Regardless of Xpert positivity, more than 80% of all cases were diagnosed of TB on chest CT by radiologists. Conclusion The detection rate of sputum Xpert MTB/RIF assay was relatively low for smear negative pulmonary TB. Chest CT image interpretation may play an important role in early diagnosis and treatment of Xpert MTB/RIF-negative pulmonary TB.

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Diagnostic challenges and Gene-Xpert utility in detecting Mycobacterium tuberculosis among suspected cases of Pulmonary tuberculosis

PLoS ONE ◽

10.1371/journal.pone.0251858 ◽

2021 ◽

Vol 16 (5) ◽

pp. e0251858

Author(s):

Shaila Kabir ◽

M. Tanveer Hossain Parash ◽

Nor Amalina Emran ◽

A. B. M. Tofazzal Hossain ◽

Sadia Choudhury Shimmi

Keyword(s):

Mycobacterium Tuberculosis ◽

Pulmonary Tuberculosis ◽

Predictive Value ◽

Demographic Data ◽

Nucleic Acid Amplification ◽

Age Group ◽

Cross Sectional ◽

Care Clinic ◽

Pulmonary Tb ◽

Smear Negative

The incidence of pulmonary tuberculosis (PTB) can be reduced by preventing transmission with rapid and precise case detection and early treatment. The Gene-Xpert MTB/RIF assay is a useful tool for detecting Mycobacterium tuberculosis (MTB) with rifampicin resistance within approximately two hours by using a nucleic acid amplification technique. This study was designed to reduce the underdiagnosis of smear-negative pulmonary TB and to assess the clinical and radiological characteristics of PTB patients. This cross-sectional study included 235 participants who went to the Luyang primary health care clinic from September 2016 to June 2017. The demographic data were analyzed to investigate the association of patient gender, age group, and ethnicity by chi-square test. To assess the efficacy of the diagnostic test, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated. The area under the curve for sputum for both AFB and gene-Xpert was analyzed to compare their accuracy in diagnosing TB. In this study, TB was more common in males than in females. The majority (50.71%) of the cases belonged to the 25–44-year-old age group and the Bajau ethnicity (57.74%). Out of 50 pulmonary TB cases (smear-positive with AFB staining), 49 samples were positive according to the Gene-Xpert MTB/RIF assay and was confirmed by MTB culture. However, out of 185 smear-negative presumptive cases, 21 cases were positive by Gene-Xpert MTB/RIF assay in that a sample showed drug resistance, and these results were confirmed by MTB culture, showing resistance to isoniazid. In comparison to sputum for AFB, Gene-Xpert showed more sensitivity and specificity with almost complete accuracy. The additional 21 PTB cases detection from the presumptive cases by GeneXpert had significant impact compared to initial observation by the routine tests which overcame the diagnostic challenges and ambiguities.

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Comparison of Auramine Phenol and ZN Staining in Diagnosis of Pulmonary Tuberculosis with GeneXpert MTB/RIF as Gold Standard

Journal of Islamabad Medical & Dental College ◽

10.35787/jimdc.v9i3.435 ◽

2020 ◽

Vol 9 (3) ◽

pp. 190-194

Author(s):

Naureen Saeed ◽

Fatima-tuz-zuhra ◽

Nadeem Ikram ◽

Farhana Shaukat ◽

Fareeha Sardar

Keyword(s):

Pulmonary Tuberculosis ◽

Positive Predictive Value ◽

Predictive Value ◽

Gold Standard ◽

Sputum Sample ◽

False Negative ◽

Smear Microscopy ◽

Predictive Values ◽

Pulmonary Tb ◽

Sensitivity Specificity

Background: Pakistan faces an immense burden of pulmonary tuberculosis (TB) due to large number of cases and limited resources. Despite the recent advancement in the diagnostic techniques for pulmonary TB, smear microscopy is still a useful technique for the diagnosis of this disease. This study was conducted in order to compare the diagnostic value of Auramine stain with the conventional Ziehl-Neelsen (ZN) stain on the sputum smear for the diagnosis of pulmonary TB, keeping GeneXpert MTB/RIF as the gold standard. Method: This cross-sectional study was conducted on 356 suspected patients of pulmonary TB referred to the Pathology laboratory from TB ward and OPD of District Head Quarter (DHQ) teaching hospital Rawalpindi, Pakistan. Sputum specimen were collected and two smears were prepared from each sputum sample on which Auramine phenol and Ziehl-Neelsen staining were carried out as per WHO recommendations. All these samples were further tested using Gene Xpert MTB/RIF technique. The sensitivity, specificity, Positive predictive value (PPV) and Negative predictive values (NPV) of ZN and Auramine stain were calculated and compared with GeneXpert MTB/RIF technique. Results: Out of the total 356 samples, 64(18%) were positive and 291(82%) were negative by GeneXpert which was taken as the gold standard. On comparison with GeneXpert, percentage of true positive was greater in case of Auramine than ZN stained samples (16.29% versus 12.92%), while the percentage of false positive was same for both staining techniques (0.28%). There were lesser false negative cases observed in samples stained by Auramine as compared to the ones stained by ZN (1.68% versus 5.05%). The sensitivity, specificity, positive predictive value and negative predictive values were 97.87%, 94.17%, 71.88 and 99.66%, respectively for the ZN staining and 98.31%, 97.98%, 90.63% and 99.66% respectively, for the Auramine phenol staining. Conclusion: Smear microscopy using Auramine phenol stain is a useful technique for the diagnosis of pulmonary TB. The Auramine phenol staining with fluorescent microscopy is found to be superior to ZN staining because of higher sensitivity and specificity. Keywords: Auramine phenol, Fluorescence microscopy, GeneXpert, Mycobacterium tuberculosis, Ziehl-Neelsen

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Real-time PCR in Bronchoalveolar Lavage Fluid in the Sputum Smear-Negative Patients Suspected of Pulmonary Tuberculosis by Chest CT

CHEST Journal ◽

10.1378/chest.10620 ◽

2010 ◽

Vol 138 (4) ◽

pp. 673A

Author(s):

Yee Hyung Kim ◽

Sohee Park ◽

Cheon Woong Choi ◽

Jee-Hong Yoo ◽

Hong Mo Kang ◽

...

Keyword(s):

Pulmonary Tuberculosis ◽

Bronchoalveolar Lavage ◽

Real Time ◽

Real Time Pcr ◽

Bronchoalveolar Lavage Fluid ◽

Lavage Fluid ◽

Chest Ct ◽

Sputum Smear ◽

Smear Negative

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Clinical characteristics and survival of patients concurrently diagnosed with lung cancer and active pulmonary tuberculosis

10.21203/rs.3.rs-279237/v1 ◽

2021 ◽

Author(s):

Hwa Young Lee ◽

Jung Won Heo ◽

Hye Seon Kang ◽

Ji Young Kang ◽

Jin Woo Kim ◽

...

Keyword(s):

Lung Cancer ◽

Pulmonary Tuberculosis ◽

Cancer Patients ◽

Clinical Characteristics ◽

Positive Culture ◽

The Body ◽

Pulmonary Tb ◽

Active Pulmonary Tuberculosis ◽

Lung Cancer Patients ◽

Clinical Stages

Abstract Background Active pulmonary tuberculosis (TB) occasionally coexists with lung cancer. However, the clinical and radiologic characteristics of this cooccurrence have not been fully evaluated. Methods Patients diagnosed with lung cancer and active pulmonary TB from January 2009 to December 2017 in four hospitals of the Catholic University of Korea were retrospectively reviewed. The clinical characteristics, including the TB diagnosis methods, lung cancer pathology, staging, initial radiographic features, and survival were analyzed and compared to 575 lung cancer patients without active pulmonary TB from the same hospitals. Results Forty-eight (0.48%) of the 9,936 lung cancer patients had active pulmonary TB confirmed by positive culture results or polymerase chain reaction analysis for M. tuberculosis at the time of the initial cancer diagnosis. The majority of the patients (95.9%) had non-small cell lung cancer and 56.2% of the lung cancers were located in the both upper lobes. In the initial computed tomography, the most frequent findings were a mass-like lesion (79.2%) and separate nodules (75%). When compared to lung cancer patients without TB, the body mass index (BMI) was lower (21.4 vs. 23.1, P = 0.001) in patients with TB. Moreover, the lung cancer patients with TB had advanced clinical stages compared to patients without TB; T3-4 (70.9% vs. 50.6%, P = 0.002), N2-3 (85.2% vs. 55.6%, P < 0.001); M1 (65.9% vs. 44.5%, P = 0.007). Patients' age, histology, location, and the presence of epidermal growth factor receptor mutations were not statistically different between the two groups. Interestingly, lung cancer with TB was associated with lower mortality (hazard ratio = 0.35, 95% CI: 0.2 1– 0.60). Conclusions Rarely diagnosed concurrent active tuberculosis in lung cancer patients was associated with lower BMI and advanced clinical stages. Active investigation of and treatment for active pulmonary TB in lung cancer patients could improve patient outcomes.

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Fluorescence microscopy for the diagnosis of smear-negative pulmonary tuberculosis in Ethiopia

African Journal of Laboratory Medicine ◽

10.4102/ajlm.v9i1.810 ◽

2020 ◽

Vol 9 (1) ◽

Author(s):

Gemeda Abebe ◽

Dossegnaw Aragaw ◽

Mulualem Tadesse

Keyword(s):

Confidence Interval ◽

Fluorescence Microscopy ◽

Pulmonary Tuberculosis ◽

Diagnostic Performance ◽

Light Emitting Diode ◽

Fluorescent Microscopy ◽

Culture Method ◽

Light Emitting ◽

Smear Negative ◽

Negative Sputum

Background: Despite its low sensitivity, microscopy remains the main method for the diagnosis of pulmonary tuberculosis in most laboratories in Ethiopia. Few studies have evaluated the performance of light-emitting diode fluorescent microscopy (LED-FM) in bleach-concentrated smear-negative sputum specimens.Objective: This study aimed to evaluate the diagnostic performance of LED-FM for smear-negative pulmonary tuberculosis in Ethiopia.Methods: A total of 194 adult patients with a cough lasting for more than two weeks, and who had three direct smear-negative sputum tests for Mycobacterium tuberculosis by Ziehl-Neelsen light microscopy, were included. All direct Ziehl-Neelsen-stained smear-negative sputum samples were cultured and were also visualised by LED-FM. Smears for LED-FM were performed from bleach-concentrated sputum sediment. The diagnostic performance of the LED-FM was compared to the culture method (the reference standard).Results: Of the 194 smear-negative sputum specimens analysed, 28 (14.4%) were culture-positive and 21 (10.8%) were LED-FM-positive for M. tuberculosis. However, only 11 of the 21 (52.4%) LED-FM-positive patients had a confirmed tuberculosis diagnosis by culture. Light-emitting diode fluorescence microscopy (FM) had a sensitivity of 39.3% (95% confidence interval: 21.2–57.4) and specificity of 93.9% (95% confidence interval: 90.4–97.6). Ten LED-FM-positive specimens were culture-negative, and all of these specimens had scanty grading (1–19 bacilli per 40 fields on LED-FM).Conclusion: This study showed that implementation of LED-FM on bleach pre-treated and concentrated sputum can significantly improve the diagnosis of smear-negative pulmonary tuberculosis. However, all scanty grade, positive smears by LED-FM need to be confirmed by reference culture method.

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Prevalence of Antibiotic Resistance to Isonicotinylhydrazide and Rifampicin in Culture Positive Pulmonary Tuberculosis Patients From 2014 to 2016 in Zahedan City, Iran

Hospital Practices and Research ◽

10.15171/hpr.2019.10 ◽

2019 ◽

Vol 4 (2) ◽

pp. 57-61

Author(s):

Seyed Mohammad Hashemi Shahri ◽

Fatemeh Fardoust ◽

Shokoufeh Mogharabi Ostad Kalayeh ◽

Mohammad Ghenaatpisheh Sanani

Keyword(s):

Antibiotic Resistance ◽

Pulmonary Tuberculosis ◽

Positive Culture ◽

Cross Sectional Study ◽

Sectional Study ◽

Cross Sectional ◽

Tuberculosis Patients ◽

Pulmonary Tb ◽

The World ◽

Culture Positive

Background: One third of the world’s population is infected with TB, and the disease is known as the second deadly global infection, even more severe than measles. The disease kills about 2 million people a year. Approximately 8 million people in the world are affected by advanced tuberculosis (TB). Objective: The current study aimed to determine the frequency of resistance to the antibiotics isoniazid and rifampin in positive culture pulmonary TB patients in Zahedan city during 2013-2016. Methods: This descriptive cross-sectional study studied 100 samples from patients who referred to Boo-Ali hospital of Zahedan city from 2014 to 2016. First, the isoniazid solution was prepared, and then the rifampin solution was prepared. After that, 200 μL of mycobacterium suspension was added to the antibiotic and antibiotic-free control. Results: Of 100 patients participating in the study, 50 (50%) were male and 50 (50%) were female. Participants had an average age of 51.69 ± 20.41 years (95-12 years), 79 (79%) were Iranians and 21 (21%) were Afghans. Of the 100 samples, 55 (55%) were from the year 2013, 21 (21%) were from 2014, 10 (10%) were from 2015, and 14 (14%) were from year 2016. The samples examined showed that 4 (4%) were resistant and 96% were sensitive. Conclusion: The results of the current study showed that out of 100 samples, 4 cases (4%) had resistance and 96% were sensitive; 2% were resistant to isoniazid, and 2% were resistant to isoniazid and rifampin.

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Retrospective Analysis of Use of Empiric Anit Tuberculosis Treatment in Smear Negative Pulmonary Tuberculosis Patients in Central Sri Lanka

SAARC Journal of Tuberculosis Lung Diseases and HIV/AIDS ◽

10.3126/saarctb.v7i2.4400 ◽

1970 ◽

Vol 7 (2) ◽

pp. 15-18

Author(s):

D Madegedara ◽

KMCN Kulathunga ◽

SC Nakandala

Keyword(s):

Sri Lanka ◽

Pulmonary Tuberculosis ◽

Mantoux Test ◽

Radiographic Findings ◽

Tuberculosis Patients ◽

Pulmonary Tb ◽

Tb Treatment ◽

Chest Clinic ◽

Group 3 ◽

Smear Negative

Objective: To critically analyze the outcome of sputum negative pulmonary TB patients who were managed in the Respiratory unit, Kandy Sri Lanka. Setting: Respiratory Unit, Teaching hospital, Kandy. Method: The subjects were between age 12 years or older and visited chest clinic Kandy, between January -December 2008 with a suspicion of pulmonary TB. 84 patients were reviewed with admission note, microbiology results and chest radiography. The characteristics of patients such as age, sex, clinical features, laboratory and radiographic findings were analyzed. Results: The diagnosis of definite or probable smear negative pulmonary TB was made on treatment outcome at one month with ATT medication. At this endpoint, 67 (79.76%) had clinical and radiological improvement, 7(8.33%) had clinical improvement and 3 (3.57%) had radiological improvement. Mantoux test was positive in 46(78%) of definite cases and 6(85.7%) in probable cases. Mycobacterial culture was positive in 5 patients. 7 (8.3%) cases were diagnosed as ‘non-TB’ based on absence of clinical / radiological improvement or discovery of another cause at or before this study end point. In non TB group 3 had carcinoma, 2 had pneumoconiosis, 1 had bronchiectasis while in 1, cause was indeterminate. Mantoux became positive in 6 (83.3%) in non Tuberculosis group. There was no association between positive Mantoux and presence of active pulmonary TB. Conclusion: Our findings suggest that empirical anti TB treatment is an acceptable practice if clinical suspicion of tuberculosis is high and patients show supportive radiological evidence of active TB. Keywords: Smear negative pulmonary tuberculosis; empirical anti tubercular treatment DOI: 10.3126/saarctb.v7i2.4400SAARC J. TUBER. LUNG DIS. HIV/AIDS 2010 VII(2) 15-18

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Role of induced sputum with hypertonic saline in the early diagnosis of no / inadequate sputum or sputum smear negative suspected cases of pulmonary tuberculosis

International Journal of Research in Medical Sciences ◽

10.18203/2320-6012.ijrms20174668 ◽

2017 ◽

Vol 5 (11) ◽

pp. 4761

Author(s):

Mayank Kapur ◽

Atul Luhadia ◽

Shanti Kumar Luhadia

Keyword(s):

Early Diagnosis ◽

Pulmonary Tuberculosis ◽

Hypertonic Saline ◽

Invasive Procedure ◽

Induced Sputum ◽

Sputum Smear ◽

Sputum Induction ◽

Pulmonary Tb ◽

Smear Negative

Background: Pulmonary Tuberculosis is one of the common infections in the world, especially in developing countries like India and is a leading cause of morbidity and mortality worldwide. Therefore, early diagnosis and microbiological confirmation of pulmonary TB is important. This study was done to assess the role of induced sputum with hypertonic saline in suspected pulmonary TB patients who produce no or inadequate sputum or who are sputum for AFB smear negative.Methods: 100 patients with clinical and radiological evidence of pulmonary TB with no or inadequate sputum or who are smear negative with spontaneous sputum were included in the study. Sputum was induced with 5ml of 3% hypertonic saline delivered through nebulizer and then was sent for Ziehl Neelsen staining examination.Results: 96 patients could produce adequate sputum after sputum induction. In 47 patients, sputum for AFB smear was found positive after induction.Conclusions: Sputum induction is a safe, cheap and non-invasive procedure and offers an alternative or additional approach in the diagnosis of sputum smear-negative suspected pulmonary tuberculosis patients and would enhance sensitivity for the diagnosis of tuberculosis.

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A Fully Automatic AI-based CT Image Analysis System for Accurate Detection, Diagnosis, and Quantitative Severity Evaluation of Pulmonary Tuberculosis

10.21203/rs.3.rs-434810/v1 ◽

2021 ◽

Author(s):

Chenggong Yan ◽

Lingfeng Wang ◽

Jie Lin ◽

Jun Xu ◽

Tianjing Zhang ◽

...

Keyword(s):

Image Analysis ◽

Pulmonary Tuberculosis ◽

Chest Ct ◽

Ct Scans ◽

Image Analysis System ◽

Imaging Features ◽

Ct Image ◽

Pulmonary Tb ◽

Ct Image Analysis ◽

Analysis System

Abstract Background: Accurate and rapid diagnosis of pulmonary tuberculosis (TB) plays a crucial role in timely prevention and appropriate medical treatment to the disease. This study aims to develop and evaluate an artificial intelligence (AI)-based fully automated CT image analysis system for detection, diagnosis, and burden quantification of pulmonary TB.Methods: From December 2007 to September 2020, 892 chest CT scans from pathogen-confirmed TB patients were retrospectively included. A deep learning based cascading framework was connected to create a processing pipeline. To train and validate the model, 1921 lesions were manually labeled, classified by six categories of critical imaging features, and visually scored for the lesion involvement as the ground truth. “TB score” was calculated by the network-activation map to assess the disease burden quantitively. Independent test datasets from two additional hospitals and NIH TB Portal were used to validate externally the performance of the AI model.Results: CT scans from 526 participants (mean age, 48.5 years±16.5; 206 women) were analyzed. The lung lesion detection subsystem yielded a mean average precision of 0.68 on the validation cohort. In the independent datasets, the overall classification accuracy for six pulmonary critical imaging findings indicative of TB were 81.08%-91.05%. A moderate to strong correlation was demonstrated between the AI model quantified “TB score” and the radiologist-estimated CT score.Conclusion: This end-to-end AI system based on chest CT can achieve human-level diagnostic performance, and holds great potential for early management and medical resource optimization of patients with pulmonary TB in clinical practice.

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Nocardiosis in HIV seropositive clinically suspected pulmonary tuberculosis patients

Tropical Doctor ◽

10.1258/td.2007.060055 ◽

2008 ◽

Vol 38 (1) ◽

pp. 34-35 ◽

Cited By ~ 9

Author(s):

M U Rasheed ◽

Getachew Belay

Keyword(s):

Respiratory Infections ◽

Positive Culture ◽

Hiv Positive ◽

Gram Stain ◽

Tuberculosis Patients ◽

Pulmonary Tb ◽

Antituberculous Treatment ◽

Lowenstein Jensen ◽

Smear Negative ◽

Hiv Seropositive

To determine the frequency of nocardiosis in HIV-positive individuals clinically suspected of having tuberculosis (TB), 140 sputum samples were collected and processed by Gram stain, modified Ziehl-Neelsen staining and by culture on Lowenstein Jensen medium. Four (2.85%) patients were positive for nocardia by microscopy and five (3.6%) had positive culture for Nocardia asterioides. In areas where HIV-associated TB is common, some patients diagnosed as smear-negative pulmonary TB will actually have nocardiosis. Clinicians should be aware of this entity in HIV/immunocompromised patients with respiratory infections who fail to respond to antituberculous treatment.

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